scholarly journals Friend or Foe: Paradoxical Roles of Autophagy in Gliomagenesis

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1411
Author(s):  
Don Carlo Ramos Batara ◽  
Moon-Chang Choi ◽  
Hyeon-Uk Shin ◽  
Hyunggee Kim ◽  
Sung-Hak Kim
Keyword(s):  
Brain Tumor ◽  
Glioblastoma Multiforme ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Primary Brain Tumor ◽  
Molecular Target ◽  
Therapeutic Strategies ◽  
Homeostatic Mechanism ◽  
Cellular Context ◽  
Cellular Components

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor in adults, with a poor median survival of approximately 15 months after diagnosis. Despite several decades of intensive research on its cancer biology, treatment for GBM remains a challenge. Autophagy, a fundamental homeostatic mechanism, is responsible for degrading and recycling damaged or defective cellular components. It plays a paradoxical role in GBM by either promoting or suppressing tumor growth depending on the cellular context. A thorough understanding of autophagy’s pleiotropic roles is needed to develop potential therapeutic strategies for GBM. In this paper, we discussed molecular mechanisms and biphasic functions of autophagy in gliomagenesis. We also provided a summary of treatments for GBM, emphasizing the importance of autophagy as a promising molecular target for treating GBM.

scholarly journals Molecular Mechanisms of Drug Resistance in Glioblastoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6385
Author(s):  
Maya A. Dymova ◽  
Elena V. Kuligina ◽  
Vladimir A. Richter
Keyword(s):  
Drug Resistance ◽  
Brain Tumor ◽  
Molecular Mechanisms ◽  
Primary Brain Tumor ◽  
Therapeutic Resistance ◽  
Molecular Characteristics ◽  
Blood Brain ◽  
Conventional Radiation ◽  
The Brain ◽  
Made In

Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and is not amenable to effective surgical resection. The present review summarizes recent advances in our understanding of the molecular mechanisms of therapeutic resistance of GBM to already known drugs, the molecular characteristics of glioblastoma cells, and the barriers in the brain that underlie drug resistance. We also discuss the progress that has been made in the development of new targeted drugs for glioblastoma, as well as advances in drug delivery across the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB).

scholarly journals PIWI-interacting RNAs and PIWI proteins in glioma: molecular pathogenesis and role as biomarkers

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Omid Reza Tamtaji ◽  
Mohammad Behnam ◽  
Mohammad Ali Pourattar ◽  
Michael R. Hamblin ◽  
Maryam Mahjoubin-Tehran ◽  
...  
Keyword(s):  
Risk Factors ◽  
Brain Tumor ◽  
Health Problem ◽  
Molecular Mechanisms ◽  
Primary Brain Tumor ◽  
Epigenetic Mechanisms ◽  
Major Health Problem ◽  
Major Health ◽  
The World ◽  
Cellular Pathways

AbstractGlioma is the most common primary brain tumor, and is a major health problem throughout the world. Today, researchers have discovered many risk factors that are associated with the initiation and progression of gliomas. Studies have shown that PIWI-interacting RNAs (piRNAs) and PIWI proteins are involved in tumorigenesis by epigenetic mechanisms. Hence, it seems that piRNAs and PIWI proteins may be potential prognostic, diagnostic or therapeutic biomarkers in the treatment of glioma. Previous studies have demonstrated a relationship between piRNAs and PIWI proteins and some of the molecular and cellular pathways in glioma. Here, we summarize recent evidence and evaluate the molecular mechanisms by which piRNAs and PIWI proteins are involved in glioma.

scholarly journals Procollagen-Like Protein as a Molecular Target in the Treatment of Primary Brain Tumor

2002 ◽  
Vol 2 ◽  
pp. 125-126
Author(s):  
Medhi Wangpaichitr ◽  
Howard Landy ◽  
Chun Jing Wu ◽  
Lynn G. Feun ◽  
Rong Xu ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Primary Brain Tumor ◽  
Molecular Target

scholarly journals NQO1 Is Regulated by PTEN in Glioblastoma, Mediating Cell Proliferation and Oxidative Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Shilin Luo ◽  
Kecheng Lei ◽  
Daxiong Xiang ◽  
Keqiang Ye
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Proliferation ◽  
Brain Tumor ◽  
Glioblastoma Multiforme ◽  
Molecular Mechanisms ◽  
Oxygen Species ◽  
Dual Roles ◽  
Dismal Prognosis ◽  
And Oxidative Stress

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a dismal prognosis, and the patients carrying EGFR-driven tumors with PTEN mutation do not respond to anti-EGFR therapy. The molecular mechanisms for this resistance remain unknown. Here, we show that PTEN induces the expression of NQO1, a flavoenzyme with dual roles in pro- and antitumorigenesis that decreases the formation of reactive oxygen species (ROS), which mediates the oxidative stress and GBM cell proliferation. NQO1 is reduced in EGFRvIII-overexpressed U87MG cells associated with low ROS, whereas NQO1 is highly escalated in PTEN stably expressed U87MG/EGFRvIII cells with high ROS. Interestingly, knockdown of NQO1 augments ROS and diminishes cell proliferation. Conversely, overexpression of NQO1 attenuates ROS and increases cell proliferation. By contrast, overexpression of PINK1, a PTEN-induced kinase 1, represses ROS and inhibits GBM cell proliferation. Therefore, our findings support that NQO1 displays a paradoxical role in mediating GBM growth in response to tumor suppressor PTEN.

scholarly journals NK Cell-Based Glioblastoma Immunotherapy

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 522 ◽  
Author(s):  
Irene Golán ◽  
Laura Rodríguez de la Fuente ◽  
Jose Costoya
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Poor Prognosis ◽  
Molecular Mechanisms ◽  
Nk Cell ◽  
High Capacity ◽  
Primary Brain Tumor ◽  
Therapeutic Approaches ◽  
Current Therapies ◽  
Cellular Components

Glioblastoma (GB) is the most aggressive and most common malignant primary brain tumor diagnosed in adults. GB shows a poor prognosis and, unfortunately, current therapies are unable to improve its clinical outcome, imposing the need for innovative therapeutic approaches. The main reason for the poor prognosis is the great cell heterogeneity of the tumor mass and its high capacity for invading healthy tissues. Moreover, the glioblastoma microenvironment is capable of suppressing the action of the immune system through several mechanisms such as recruitment of cell modulators. Development of new therapies that avoid this immune evasion could improve the response to the current treatments for this pathology. Natural Killer (NK) cells are cellular components of the immune system more difficult to deceive by tumor cells and with greater cytotoxic activity. Their use in immunotherapy gains strength because they are a less toxic alternative to existing therapy, but the current research focuses on mimicking the NK attack strategy. Here, we summarize the most recent studies regarding molecular mechanisms involved in the GB and immune cells interaction and highlight the relevance of NK cells in the new therapeutic challenges.

scholarly journals Challenges in Immunotherapy Presented by the Glioblastoma Multiforme Microenvironment

2011 ◽  
Vol 2011 ◽  
pp. 1-20 ◽  
Author(s):  
Christopher Jackson ◽  
Jacob Ruzevick ◽  
Jillian Phallen ◽  
Zineb Belcaid ◽  
Michael Lim
Keyword(s):  
Brain Tumor ◽  
Glioblastoma Multiforme ◽  
Tumor Microenvironment ◽  
Median Survival ◽  
Immune Surveillance ◽  
Cell Types ◽  
Primary Brain Tumor ◽  
Cellular Level ◽  
Significant Challenge ◽  
Multiple Signaling

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. Despite intensive treatment, the prognosis for patients with GBM remains grim with a median survival of only 14.6 months. Immunotherapy has emerged as a promising approach for treating many cancers and affords the advantages of cellular-level specificity and the potential to generate durable immune surveillance. The complexity of the tumor microenvironment poses a significant challenge to the development of immunotherapy for GBM, as multiple signaling pathways, cytokines, and cell types are intricately coordinated to generate an immunosuppressive milieu. The development of new immunotherapy approaches frequently uncovers new mechanisms of tumor-mediated immunosuppression. In this review, we discuss many of the current approaches to immunotherapy and focus on the challenges presented by the tumor microenvironment.

scholarly journals Reuse of Molecules for Glioblastoma Therapy

2021 ◽  
Vol 14 (2) ◽  
pp. 99
Author(s):  
Abigail Koehler ◽  
Aniruddha Karve ◽  
Pankaj Desai ◽  
Jack Arbiser ◽  
David R. Plas ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Glioblastoma Multiforme ◽  
Standard Of Care ◽  
Primary Brain Tumor ◽  
Clinical Use ◽  
Current Standard ◽  
Non Invasive ◽  
Tumor Treating Fields ◽  
Emerging Treatments ◽  
Stupp Protocol

Glioblastoma multiforme (GBM) is a highly malignant primary brain tumor. The current standard of care for GBM is the Stupp protocol which includes surgical resection, followed by radiotherapy concomitant with the DNA alkylator temozolomide; however, survival under this treatment regimen is an abysmal 12–18 months. New and emerging treatments include the application of a physical device, non-invasive ‘tumor treating fields’ (TTFs), including its concomitant use with standard of care; and varied vaccines and immunotherapeutics being trialed. Some of these approaches have extended life by a few months over standard of care, but in some cases are only available for a minority of GBM patients. Extensive activity is also underway to repurpose and reposition therapeutics for GBM, either alone or in combination with the standard of care. In this review, we present select molecules that target different pathways and are at various stages of clinical translation as case studies to illustrate the rationale for their repurposing-repositioning and potential clinical use.

GLIOBLASTOMA MULTIFORME: PATHOGENESIS AND MOLECULAR MARKERS

2017 ◽  
Vol 63 (5) ◽  
pp. 695-702
Author(s):  
Oleg Kit ◽  
Dmitriy Vodolazhskiy ◽  
Yelena Frantsiyants ◽  
Svetlana Panina ◽  
E. Rastorguev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Tumor ◽  
Molecular Markers ◽  
Glioblastoma Multiforme ◽  
Somatic Mutations ◽  
Web Of Science ◽  
Molecular Subtypes ◽  
Regulation Of Gene Expression ◽  
Signal Pathways ◽  
Poorly Differentiated

Glioblastoma multiforme (GBM) is the most common and invasive poorly differentiated brain tumor with nearly 100 % rate of recurrence and unfavorable prognosis. The aim of the present review is to analyze recent studies and experimental results (Scopus, Web of Science, PubMed) concerning somatic mutations in glioblastoma, aberrant regulation of gene expression of signal pathways including EGFR, TGFß, etc. and markers for GBM progression. Particularly the molecular subtypes of glioblastoma and NGS results are considered in this review.

Natural Products for Regulating Macrophages M2 Polarization

2020 ◽  
Vol 15 (7) ◽  
pp. 559-569 ◽  
Author(s):  
Zhen Chang ◽  
Youhan Wang ◽  
Chang Liu ◽  
Wanli Smith ◽  
Lingbo Kong
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Therapeutic Strategies ◽  
Research Progress ◽  
Cellular Mechanisms ◽  
Pharmacological Activities ◽  
Current Review ◽  
M2 Polarization ◽  
Macrophages Polarization ◽  
Herbal Plants

Macrophages M2 polarization have been taken as an anti-inflammatory progression during inflammation. Natural plant-derived products, with potential therapeutic and preventive activities against inflammatory diseases, have received increasing attention in recent years because of their whole regulative effects and specific pharmacological activities. However, the molecular mechanisms about how different kinds of natural compounds regulate macrophages polarization still unclear. Therefore, in the current review, we summarized the detailed research progress on the active compounds derived from herbal plants with regulating effects on macrophages, especially M2 polarization. These natural occurring compounds including flavonoids, terpenoids, glycosides, lignans, coumarins, alkaloids, polyphenols and quinones. In addition, we extensively discussed the cellular mechanisms underlying the M2 polarization for each compound, which could provide potential therapeutic strategies aiming macrophages M2 polarization.

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